[unreadable] The broad, long-term objective of this proposal is to improve the health and quality of life of patients with primary biliary cirrhosis (PBC) and other disorders that cause pruritus. The immediate, short-term objective of this proposal is to determine the safety and efficacy of sertraline as a treatment for cholestatic pruritus. The hypothesis of this proposal, which is based on the previous observation that some patients with PBC have experienced resolution of their pruritus when given sertraline, is that sertraline therapy will improve the symptom of cholestatic pruritus. The specific aims are: 1) to determine the optimal dose and time to response of sertraline treatment for cholestatic pruritus 2) to determine the tolerability of sertraline in patients with reduced liver function. The secondary aims of this proposal will be to evaluate the effect of sertraline on cholestatic pruritus and to determine how changes in pruritus are related to changes in depressive symptoms or plasma sertraline/desmethylsertraline levels. The health relatedness of the project is the potential to identify an innovative, more effective, and better-tolerated treatment of cholestatic pruritus. Patients with cholestatic liver disease often suffer from disabling pruritus. Current treatments are not always effective, and liver transplantation is sometimes necessary to alleviate the pruritus. Quality of life is significantly impaired by chronic pruritus. The method to be used in the proposal is a clinical therapeutic trial of sertraline in patients with pruritus due to either PBC or chronic hepatitis C. The research design is divided into two parts. In first part (A), subjects with cholestatic pruritus will undergo an unblinded dose escalation of sertraline. Part B of the study will consist of a double-blind, randomized, placebo-controlled, crossover study of the efficacy of sertraline. Data regarding pruritus symptoms and side effects of sertraline will be collected and analyzed to determine the safety and efficacy of sertraline used in this setting. These studies will serve as pilot trials. The results of this proposed project will be used to design a larger controlled trial that could be proposed for funding through an R01 mechanism. [unreadable] [unreadable]